While the anticonvulsants ethosuximide and valproate have wisespread clinical use as antiepileptic drugs, their effect on primary excitable membrane processes has heretofore not been studied extensively. Using the squid giant axon as a model experimental system for the study of sodium and potassium channels, voltage clamp studies were carried out to test the effects of these agents on excitability. Both studies were carried out to test the effects of these agents on excitability. Both gating current and ionic currents were measured. Ethosuximide was shown to be an extenal voltage-independent on both gating and open channel conductance. When applied internally both ethosuximide and valproate slow sodium channel gating, but valproate slows K channel gating without effect on the flux through open channels. These results suggest that both of these agents may have therapeutic properties directly at the membrane level that are unrelated to their synaptic effects.